NFE2L2 and Hyperglycemia: The expression of Nrf2 and its downstream genes is slightly increased in the cardiovascular systems of STZ-induced T1DM mice at 2–3months after the onset of hyperglycemia, but then becomes significantly downregulated at 5–6months after the development of hyperglycemia (Tan et al., 2011; Miao et al., 2012; Bai et al., 2013), suggesting the burnout of an important redox protective mechanism in the advanced stages of DM.